Is Bilirubin Associated with the Severity of Ischemic Stroke? A Dose Response Meta-Analysis.
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SUBMITTER: Song Y
PROVIDER: S-EPMC9224549 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
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Is Bilirubin Associated with the Severity of Ischemic Stroke? A Dose Response Meta-Analysis.
Song Yumeng Y Zhang Xiaohong X Li Chaoxiu C Xu Shuang S Zhou Baosen B Wu Xiaomei X
Journal of clinical medicine 20220607 12
There is no consensus on the role of bilirubin in acute ischemic stroke. Higher levels of serum bilirubin may provide a treatment advantage in oxidative-stress-mediated diseases but also may simply reflect the strength of the oxidative stress. As of 28 February 2022, the relevant studies were selected from four databases (PubMed, Web of science, Cochrane, and CNKI) through a retrieval strategy, and strict literature screening and quality evaluation were carried out. The dose-response relationshi ...[more]
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Project description:BackgroundAlthough trimethylamine-N-oxide (TMAO) shows a notable correlation with cardiovascular disease, its association with acute ischemic stroke (AIS) remains uncertain and necessitates further investigation.ObjectiveA meta-analysis was conducted to assess the relationship between trimethylamine-N-oxide and acute ischemic stroke.MethodsWe conducted a comprehensive search in PubMed, Embase, Cochrane, CNKI, VIP, Wanfang, and CBM, spanning from their inception to 23 September 2023. The search was consistently updated and supplemented by bibliographies of retrieved articles and previous reviews. A total of 20 eligible studies, including 17 case‒controls and 3 cohort studies, were selected, involving 9141 participants (5283 case group, 3858 control group). For the dose‒response analysis, three case-control studies were eligible. We extracted and pooled TMAO mean and standard deviation from observational studies for control and ischemic stroke groups. The effect sizes were combined using the random-effects model. Where possible, dose‒response analysis was performed.ResultOverall, the pooled standardized mean difference (SMD) demonstrated significantly higher concentrations of serum/plasma TMAO in AIS compared to the control group (SMD = 1.27; 95% CI: 0.9, 1.61, P<0.001). Additionally, the dose‒response meta-analysis revealed a 12.1% relative increase in the risk of acute ischemic stroke per 1 μmol/L rise in TMAO concentration (RR = 1.12; 95% CI 1.07-1.17; P<0.05; I2 = 1.6%, P = 0.4484).ConclusionThese findings indicate a potential increased risk of AIS associated with elevated TMAO levels.
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Project description:BackgroundCirculating total bilirubin is a biomarker of ischemic stroke and may serve as a potential prognostic factor. It is imperative to systemically evaluate the correlation between circulating total bilirubin and risk for stroke. This systematic review and meta-analysis investigated the relationship between total serum bilirubin and risk for stroke.MethodsStudies published before 30 June 2017 were searched in four databases (PubMed, EMBASE, Web of Science and Cochrane Central). Additional studies were searched by reviewing references and contacting authors. Cohort, cross-sectional and case-control studies in adults that examined the association between serum total bilirubin and stroke were included irrespective of language and date of publication. The primary outcome of this study was ischemic stroke, and the secondary outcome was stroke. Abstract and full-text were reviewed by two independent reviewers, and disagreement was resolved by consulting a third reviewer. Data were extracted by two independent reviewers using a pre-designed data collection form.ResultsEleven observational studies (5 prospective and 6 cross-sectional studies) involving 131,450 subjects were included for analysis. In four studies with 83,380 subjects, the relationship between circulating total bilirubin and ischemic stroke was investigated, ischemic stroke was found in 2,496 patients, and the total odds ratio (OR) of the highest bilirubin and the lowest bilirubin for the occurrence of ischemic stroke was 0.66 (95% CI: 0.58-0.74). Eleven studies with 131,450 subjects explored the correlation between bilirubin and stroke, stroke was reported in 5,060 patients, and the total OR of the highest bilirubin and the lowest bilirubin for the occurrence of stroke was 0.73 (95% CI: 0.68-0.79). A stratified analysis based on the gender showed that the total bilirubin level in males correlated with ischemic stroke or stroke, which was not noted in females.ConclusionsThe available studies support an inverse association between circulating total bilirubin and risk for ischemic stroke and stroke in males. Prospective studies with large sample size are needed to establish the role of circulating bilirubin in the prevention of stroke.
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Project description:BackgroundThe prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties. We aimed to investigate the association between serum bilirubin, including total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) and poor functional outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).MethodsAll patients with AIS or TIA were recruited from the Third China National Stroke Registry. The poor functional outcomes included modified Rankin Scale (mRS) score 2-6 and 3-6 at 3 months and 1 year. Multivariable logistic regression was used to investigate the associations of TBIL, DBIL, and IBIL with poor functional outcomes.ResultsAmong 11,121 enrolled patients, the median (interquartile range) of TBIL, DBIL, and IBIL was 13.30 (9.90-17.70), 3.80 (2.70-5.30), and 9.30 (6.70-12.80) µmol/L. After adjustment for conventional confounding factors, patients in the highest TBIL quartile had the highest proportion of mRS score 2-6 at 3 months (odds ratio [OR], 1.37; 95 % confidence interval [CI], 1.19-1.59) and 1 year (OR, 1.31; 95 % CI, 1.13-1.52), and mRS score 3-6 at 3 months (OR, 1.33; 95 % CI, 1.11-1.59) and 1 year (OR, 1.28; 95 % CI, 1.07-1.53), when compared to patients in the lowest TBIL quartile. Similar results were observed for DBIL and IBIL. We also found J-shaped associations between serum bilirubin levels and each outcome.ConclusionsElevated levels of serum bilirubin were significantly associated with poor functional outcomes in patients with AIS or TIA at 3 months and 1 year.
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Project description:BackgroundCoronavirus disease 2019 (COVID-19), a contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the world. Apart from respiratory complications, an increasing number of patients with ischemic stroke have been reporting.ObjectiveThis systematic review and meta-analysis aims to explore the characteristics of ischemic stroke after SARS-CoV-2 infection, and provides valuable reference materials for subsequent clinical treatment.Materials and methodsPubMed, Web of Science, and Ovid-Embase databases were searched up to 24th March 2021. We utilized the search strategy of medical subject headings combined with entry terms to search all related literatures. All studies identified with the electronic and manual searches were listed by citation, title, authors, and abstract. Only studies involving patients with COVID-19-related stroke were eligible. The references of included studies were also manually screened.ResultsThe meta-analysis was conducted following the PRISMA and MOOSE reporting guidelines. Bias risk was assessed using the Newcastle-Ottawa Scale (NOS). Ten articles, including 26,691 participants and 280 patients with ischemic stroke and COVID-19, were selected. The pooled prevalence of ischemic stroke in COVID-19 was 2% (95% CI 1-2%; p < 0.01). The pooled proportions of hypertension, hyperlipidemia and diabetes in COVID-19-related ischemic stroke was 66% (95% CI 51-81%; p < 0.01), 48% (95% CI 19-76%; p < 0.01) and 40% (95% CI 29-51%; p < 0.01), respectively. Notably, the pooled proportions of female was 36% (95% CI 21-50%; p < 0.01) in patients with COVID-19 and stroke. In addition, in TOAST classification, cryptogenic stroke subtype was associated with a high trend, and its pooled proportion was 35% (95% CI 12-59%; p < 0.01).ConclusionIschemic stroke caused by COVID-19 has its own unique clinical features. Although common high-risk factors can also be observed, its importance may have changed. The major inflammatory storm of COVID-19 is more likely to occur in male patients. The increase in the proportion of cryptogenic stroke has also made stroke related to COVID-19 complicated.
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Project description:ObjectivesPrevious research has predominantly focused on total bilirubin levels without clearly distinguishing between direct and indirect bilirubin. In this study, the differences between these forms were examined, and their potential causal relationships with ischemic stroke were investigated.MethodsTwo-sample multivariable Mendelian randomization (MVMR) analysis was employed, extracting summary data on bilirubin from the Korean Cancer Prevention Study-II (n=159,844) and the Korean Genome and Epidemiology Study (n=72,299). Data on ischemic stroke were obtained from BioBank Japan (n=201,800). Colocalization analysis was performed, focusing on the UGT1A1, SLCO1B1, and SLCO1B3 genes, which are the primary loci associated with serum bilirubin levels.ResultsCrude 2-sample Mendelian randomization analysis revealed a significant negative association between total bilirubin levels and ischemic stroke. However, in MVMR analyses, only indirect bilirubin demonstrated a significant negative association with ischemic stroke (odds ratio, 0.76; 95% confidence interval, 0.59 to 0.98). Colocalization analysis did not identify a shared causal variant between the 3 genetic loci related to indirect bilirubin and the risk of ischemic stroke.ConclusionsOur study establishes a causal association between higher genetically determined levels of serum indirect bilirubin and reduced risk of ischemic stroke in an Asian population. Future research should include more in-depth analysis of shared genetic variants between indirect bilirubin and ischemic stroke.
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Project description:ObjectiveBilirubin has anti-inflammatory, antioxidant, and neuroprotective properties, but the association between bilirubin and stroke remains contentious. A meta-analysis of extensive observational studies on the relationship was conducted.MethodsStudies published before August 2022 were searched in PubMed, EMBASE, and Cochrane Library. Cohort, cross-sectional and case-control studies that examined the association between circulating bilirubin and stroke were included. The primary outcome included the incidence of stroke and bilirubin quantitative expression level between stroke and control, and the secondary outcome was stroke severity. All pooled outcome measures were determined using random-effects models. The meta-analysis, subgroup analysis, and sensitivity analysis were performed using Stata 17.ResultsA total of 17 studies were included. Patients with stroke had a lower total bilirubin level (mean difference = -1.33 μmol/L, 95% CI: -2.12 to -0.53, P < 0.001). Compared with the lowest bilirubin level, total odds ratio (OR) of the highest bilirubin for the occurrence of stroke was 0.71 (95% CI: 0.61-0.82) and ischemic stroke was 0.72 (95% CI: 0.57-0.91), especially in cohort studies with accepted heterogeneity (I 2 = 0). Serum total and direct bilirubin levels were significantly and positively associated with stroke severity. A stratified analysis based on gender showed that the total bilirubin level in males correlated with ischemic stroke or stroke, which was not noted in females.ConclusionWhile our findings suggest associations between bilirubin levels and stroke risk, existing evidence is insufficient to establish a definitive association. Better-designed prospective cohort studies should further clarify pertinent questions (PROSPERO registration number: CRD42022374893).
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